Higher Doses of 'Abortion Pill' Safe in Cushing's?

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Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

In an open label study, the use of higher doses of mifepristone, a glucocorticoid receptor antagonist formerly known as RU-486, was associated with clinical response but not increased occurrence of adverse effects.

Clinicians participating in the trial were told they could titrate beyond the starting dose of 300 mg a day. To look at the relationship between dose and safety, as well as response, Nguyen and colleagues looked at data on 40 of the patients who responded to therapy.

Most of them (90%) were taking at least 600 mg a day, 68% were taking at least 900 mg per day, and 44% took 1,200 mg daily.

Most of the responders (85%) had their initial clinical response at a dose of at least 600 mg daily.

Overall, there were 26 serious adverse events:

10 at the 300 mg dose

8 at the 600 mg dose

3 at the 900 mg dose

3 at the 1200 mg dose

2 while off drug

When the researchers adjusted for the number of patients who had ever reached a given dose, the frequency of serious adverse events was similar across doses:

10% of patients at 300 mg

16% of patients at 600 mg

15% of patients at 900 mg

14% of patients at 1200 mg

The four most common adverse events decreased after week 10 – although that tracked an increase in dose (mean 588 mg/day before week 10 versus 895 mg/day thereafter).

Nguyen and colleagues concluded that higher doses of mifepristone weren't associated with increases in serious adverse events or in the most common adverse events – and that better response was seen with higher doses.

Korlym was developed by Corcept Therapeutics of Menlo Park, Calif., as an orphan drug given that it is is believed only 5,000 patients are eligible for treatment. That gave the company 7 years of exclusive rights to market the agent for Cushing's disease.

The label limits the drug's indication to patients with endogenous Cushing's disease who have type 2 diabetes or glucose intolerance and aren't candidates for surgery, or failed to respond to surgical intervention.

The drug doesn't reduce cortisol production but prevents it from binding to its receptor – an action separate from its blockade of the progesterone receptor, which makes it an effective agent in abortion.

Since the daily doses are in the same range as those used to induce abortion, the drug is contraindicated in pregnant women. It also carries a boxed warning that the drug will terminate a pregnancy.

Nguyen reported no relevant financial disclosures.

Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania

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